Paroxysmal Nocturnal Hemoglobinuria (PNH)
Conditions
Keywords
Paroxysmal nocturnal hemoglobinuria, Hemoglobin, Anemia, LNP023, Iptacopan
Brief summary
The purpose of this Phase 3 study was to determine whether iptacopan is efficacious and safe for the treatment of Paroxysmal nocturnal hemoglobinuria (PNH) patients who were naïve to complement inhibitor therapy.
Detailed description
This study was a multicenter, single-arm, open-label trial which was comprised of 8 weeks screening period, 24-week core treatment period and 24-week extension treatment period. Eligible PNH patients with hemolysis (LDH \> 1.5 ULN) and anemia (hemoglobin \<10 g/dL), who were naive to complement inhibitor therapy, including anti-C5 antibody treatment, received iptacopan monotherapy at a dose 200 mg orally b.i.d.
Interventions
Taken orally b.i.d. Dosage supplied: 200mg Dosage form: Hard gelatin capsule Route of Administration: oral
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female participants ≥ 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with RBCs and WBCs clone size ≥ 10% * Mean hemoglobin level \<10 g/dL * LDH \> 1.5 x Upper Limit of Normal (ULN) * Vaccination against Neisseria meningitidis infection is required prior to the start of study treatment * If not received previously, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given
Exclusion criteria
* Prior treatment with a complement inhibitor, including anti-C5 antibody * Known or suspected hereditary complement deficiency * History of hematopoietic stem cell transplantation * Patients with laboratory evidence of bone marrow failure (reticulocytes \<100x109/L; platelets \<30x109/L; neutrophils \<0.5x109/L). * Active systemic bacterial, viral (incl. COVID-19)or fungal infection within 14 days prior to study drug administration. * History of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus. * Major concurrent comorbidities including but not limited to severe kidney disease (e.g., dialysis), advanced cardiac disease (e.g., NYHA class IV heart failure), severe pulmonary disease (e.g., severe pulmonary hypertension (WHO class IV)), or hepatic disease (e.g., active hepatitis) that in the opinion of the investigator precludes participant's participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Marginal Proportion (Expressed as Percentage) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions | Baseline, hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168 | Sustained increase in hemoglobin levels (responder) is defined as an increase from baseline in hemoglobin levels of ≥ 2 g/dL on three out of four measurements between Day 126 and 168 of the core treatment period, without requiring red blood cell (RBC) transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the primary analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Annualized Major Adverse Vascular Events Rate in the Core Treatment Period | Between Day 1 and Day 168 | Adjusted annual rate is carried out using the Wilson method. A MAVE is defined as: acute peripheral vascular occlusion, amputation (non-traumatic; nondiabetic), cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, dermal thrombosis, gangrene (non-traumatic; nondiabetic), hepatic/portal vein thrombosis (Budd-Chiari syndrome), mesenteric/visceral arterial, thrombosis or infarction, mesenteric/visceral vein thrombosis or infarction, myocardial infarction, pulmonary embolus, renal arterial thrombosis, renal vein thrombosis, thrombophlebitis / deep vein thrombosis, transient ischemic attack, unstable angina or other. |
| Change From Baseline in FACIT-Fatigue Score | Baseline and mean of visits between Day 126 and Day 168 | Change from baseline in FACIT-Fatigue scores as mean of visits between Day 126 and Day 168. The FACIT-Fatigue is a 13-item questionnaire with support for its validity and reliability in PNH that assesses patient self-reported fatigue and its impact on daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-F Scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best. Change from baseline was analyzed using a Mixed Model of Repeated Measures (MMRM) which includes age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, baseline FACIT-Fatigue score as fixed effects and visit\*baseline FACIT-Fatigue score as interaction. |
| Marginal Proportion (Expressed as Percentage) With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions | Hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168 | Sustained hemoglobin levels (responder) is defined as hemoglobin levels ≥ 12 g/dL on three out of four measurements between Day 126 and 168 of the core treatment period, without requiring red blood cell (RBC) transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the analysis. |
| Marginal Proportion (Expressed as Percentage) of Participants Who Remain Free From Transfusions | Between Day 14 and Day 168 | Marginal proportion (expressed as percentage) of participants who did not require transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. The 95% CI was obtained using the bootstrap method |
| Change From Baseline in Hemoglobin Levels in the Core Treatment Period | Baseline, Day 126 to 168 | Change from baseline in hemoglobin levels as mean of visits between Day 126 and Day 168. In order to factor out the effect of transfusions in this analysis, if a patient had a transfusion during the core treatment period, the hemoglobin (Hb) values during 30 days following the transfusion were excluded and Hb data were imputed. Change from baseline was analyzed using a mixed model of repeated measures which included age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, and baseline hemoglobin as fixed effects and the interaction between visit and baseline hemoglobin levels. |
| Percent Change From Baseline in LDH | Baseline, Day 126 to 168 | Percent change from baseline in lactate dehydrogenase (LDH) levels as mean of visits between Day 126 and Day 168. Percentage change from baseline was analyzed using a mixed model for repeated measures (MMRM) which includes age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, baseline LDH as fixed effects and visit\*baseline LDH as interaction. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the analysis. |
| Adjusted Annualized Clinical BTH Rate in the Core Treatment Period | Between Day 1 and Day 168 | Adjusted annualized rate of clinical breakthrough hemolysis (BTH) events is carried out using the Wilson method. The breakthrough is defined clinical if either there is a decrease in hemoglobin levels equal to or more than 2 g/dL (compared to the latest assessment, or within 15 days) or if patients present signs or symptoms of gross hemoglobinuria, painful crisis, dysphagia or any other significant clinical PNH-related signs & symptoms, in presence of laboratory evidence of intravascular hemolysis. |
| Change From Baseline in Absolute Reticulocyte Count | Baseline and mean of visits between Day 126 and 168 | Change from baseline in absolute reticulocyte counts as mean of visits between Day 126 and Day 168. Change from baseline was analyzed using a MMRM which includes age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, baseline reticulocyte counts as fixed effects and visit\*baseline reticulocyte counts as interaction. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in LDH at Visit Day 336 | Baseline, Day 336 | Change from baseline in Lactate dehydrogenase (LDH) at Visit Day 336 |
| Percentage of Patients Meeting Hematological Response Criteria Irrespective of RBC Transfusions | Baseline, Day 336 | Patients with hematological response are those with an increase in Hb from baseline ≥ 2g/dL irrespective of red blood cell (RBC) transfusions and patients achieving Hb ≥ 12g/dL irrespective of RBC transfusions. |
| Marginal Proportion (Expressed as Percentage) of Patients Not Receiving and Not Requiring RBC Transfusions | Between Day 14 and Day 336 | Requiring Red Blood Cells (RBC) transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). |
| Adjusted Annualized Clinical BTH Rate After the Start of LNP023 Treatment | Between Day 1 and Day 336 | Adjusted annualized rate of clinical breakthrough hemolysis (BTH) events is carried out using the Wilson method. The breakthrough is defined clinical if either there is a decrease in hemoglobin levels equal to or more than 2 g/dL (compared to the latest assessment, or within 15 days) or if patients present signs or symptoms of gross hemoglobinuria, painful crisis, dysphagia or any other significant clinical PNH-related signs & symptoms, in presence of laboratory evidence of intravascular hemolysis. |
| Change From Baseline in Absolute Reticulocyte Count at Day 336 | Baseline, Day 336 | Change from baseline in absolute reticulocyte count at visit Day 336. |
| Change From Baseline in FACIT-Fatigue Score | Baseline, Day 336 | The FACIT-Fatigue is a 13-item questionnaire with support for its validity and reliability in PNH that assesses patient self-reported fatigue and its impact on daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-F Scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best. |
| Adjusted Annualized Major Adverse Vascular Events Rate After the Start of LNP023 Treatment | Between Day 1 and Day 336 | Adjusted annual rate is carried out using the Wilson method. A Major Adverse Vascular Events (MAVE) is defined as: acute peripheral vascular occlusion, amputation (non-traumatic; nondiabetic), cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, dermal thrombosis, gangrene (non-traumatic; nondiabetic), hepatic/portal vein thrombosis (Budd-Chiari syndrome), mesenteric/visceral arterial, thrombosis or infarction, mesenteric/visceral vein thrombosis or infarction, myocardial infarction, pulmonary embolus, renal arterial thrombosis, renal vein thrombosis, thrombophlebitis / deep vein thrombosis, transient ischemic attack, unstable angina or other |
| Change From Baseline in Hemoglobin Levels | Baseline, Day 336 | Change from baseline in Hemoglobin at Visit Day 336 |
Countries
China, France, Germany, Italy, Malaysia, Singapore, South Korea, United Kingdom
Participant flow
Recruitment details
Participants took part in 12 investigative sites in 8 countries: France(1), United Kingdom(1), Italy(1), Korea, Republic of(1), Singapore(1), China(3), Malaysia(2), Germany(2)
Pre-assignment details
All patients provided written informed consent prior to the start of any study-related activities. Vaccination against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections was required prior to the start of treatment.
Participants by arm
| Arm | Count |
|---|---|
| LNP023 Participants receive LNP023 at a dose of 200 mg b.i.d. orally | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | LNP023 |
|---|---|
| Age, Continuous | 42.1 years STANDARD_DEVIATION 15.85 |
| Race/Ethnicity, Customized Asian | 27 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized White | 12 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 40 |
| other Total, other adverse events | 24 / 40 |
| serious Total, serious adverse events | 8 / 40 |
Outcome results
Primary
Marginal Proportion (Expressed as Percentage) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions
Sustained increase in hemoglobin levels (responder) is defined as an increase from baseline in hemoglobin levels of ≥ 2 g/dL on three out of four measurements between Day 126 and 168 of the core treatment period, without requiring red blood cell (RBC) transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the primary analysis.
Time frame: Baseline, hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LNP023 | Marginal Proportion (Expressed as Percentage) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions | 92.2 Percentage of responders |
Secondary
Adjusted Annualized Clinical BTH Rate in the Core Treatment Period
Adjusted annualized rate of clinical breakthrough hemolysis (BTH) events is carried out using the Wilson method. The breakthrough is defined clinical if either there is a decrease in hemoglobin levels equal to or more than 2 g/dL (compared to the latest assessment, or within 15 days) or if patients present signs or symptoms of gross hemoglobinuria, painful crisis, dysphagia or any other significant clinical PNH-related signs & symptoms, in presence of laboratory evidence of intravascular hemolysis.
Time frame: Between Day 1 and Day 168
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LNP023 | Adjusted Annualized Clinical BTH Rate in the Core Treatment Period | 0.00 BTH events/year |
Secondary
Adjusted Annualized Major Adverse Vascular Events Rate in the Core Treatment Period
Adjusted annual rate is carried out using the Wilson method. A MAVE is defined as: acute peripheral vascular occlusion, amputation (non-traumatic; nondiabetic), cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, dermal thrombosis, gangrene (non-traumatic; nondiabetic), hepatic/portal vein thrombosis (Budd-Chiari syndrome), mesenteric/visceral arterial, thrombosis or infarction, mesenteric/visceral vein thrombosis or infarction, myocardial infarction, pulmonary embolus, renal arterial thrombosis, renal vein thrombosis, thrombophlebitis / deep vein thrombosis, transient ischemic attack, unstable angina or other.
Time frame: Between Day 1 and Day 168
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LNP023 | Adjusted Annualized Major Adverse Vascular Events Rate in the Core Treatment Period | 0.00 MAVE events/year |
Secondary
Change From Baseline in Absolute Reticulocyte Count
Change from baseline in absolute reticulocyte counts as mean of visits between Day 126 and Day 168. Change from baseline was analyzed using a MMRM which includes age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, baseline reticulocyte counts as fixed effects and visit\*baseline reticulocyte counts as interaction.
Time frame: Baseline and mean of visits between Day 126 and 168
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LNP023 | Change From Baseline in Absolute Reticulocyte Count | -82.48 x10^9 cells/L |
Secondary
Change From Baseline in FACIT-Fatigue Score
Change from baseline in FACIT-Fatigue scores as mean of visits between Day 126 and Day 168. The FACIT-Fatigue is a 13-item questionnaire with support for its validity and reliability in PNH that assesses patient self-reported fatigue and its impact on daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-F Scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best. Change from baseline was analyzed using a Mixed Model of Repeated Measures (MMRM) which includes age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, baseline FACIT-Fatigue score as fixed effects and visit\*baseline FACIT-Fatigue score as interaction.
Time frame: Baseline and mean of visits between Day 126 and Day 168
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LNP023 | Change From Baseline in FACIT-Fatigue Score | 10.75 score on a scale |
Secondary
Change From Baseline in Hemoglobin Levels in the Core Treatment Period
Change from baseline in hemoglobin levels as mean of visits between Day 126 and Day 168. In order to factor out the effect of transfusions in this analysis, if a patient had a transfusion during the core treatment period, the hemoglobin (Hb) values during 30 days following the transfusion were excluded and Hb data were imputed. Change from baseline was analyzed using a mixed model of repeated measures which included age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, and baseline hemoglobin as fixed effects and the interaction between visit and baseline hemoglobin levels.
Time frame: Baseline, Day 126 to 168
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LNP023 | Change From Baseline in Hemoglobin Levels in the Core Treatment Period | 4.28 g/dL |
Secondary
Marginal Proportion (Expressed as Percentage) of Participants Who Remain Free From Transfusions
Marginal proportion (expressed as percentage) of participants who did not require transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. The 95% CI was obtained using the bootstrap method
Time frame: Between Day 14 and Day 168
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LNP023 | Marginal Proportion (Expressed as Percentage) of Participants Who Remain Free From Transfusions | 97.6 Percentage of participants |
Secondary
Marginal Proportion (Expressed as Percentage) With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions
Sustained hemoglobin levels (responder) is defined as hemoglobin levels ≥ 12 g/dL on three out of four measurements between Day 126 and 168 of the core treatment period, without requiring red blood cell (RBC) transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the analysis.
Time frame: Hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LNP023 | Marginal Proportion (Expressed as Percentage) With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions | 62.8 Percentage of responders |
Secondary
Percent Change From Baseline in LDH
Percent change from baseline in lactate dehydrogenase (LDH) levels as mean of visits between Day 126 and Day 168. Percentage change from baseline was analyzed using a mixed model for repeated measures (MMRM) which includes age (indicator variable of age ≥ 45 years), sex, history of transfusion (yes/no) prior to study treatment, visit, baseline LDH as fixed effects and visit\*baseline LDH as interaction. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the analysis.
Time frame: Baseline, Day 126 to 168
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LNP023 | Percent Change From Baseline in LDH | -83.55 Percent change from baseline in LDH |
Other Pre-specified
Adjusted Annualized Clinical BTH Rate After the Start of LNP023 Treatment
Adjusted annualized rate of clinical breakthrough hemolysis (BTH) events is carried out using the Wilson method. The breakthrough is defined clinical if either there is a decrease in hemoglobin levels equal to or more than 2 g/dL (compared to the latest assessment, or within 15 days) or if patients present signs or symptoms of gross hemoglobinuria, painful crisis, dysphagia or any other significant clinical PNH-related signs & symptoms, in presence of laboratory evidence of intravascular hemolysis.
Time frame: Between Day 1 and Day 336
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LNP023 | Adjusted Annualized Clinical BTH Rate After the Start of LNP023 Treatment | 0.05 BTH events/year |
Other Pre-specified
Adjusted Annualized Major Adverse Vascular Events Rate After the Start of LNP023 Treatment
Adjusted annual rate is carried out using the Wilson method. A Major Adverse Vascular Events (MAVE) is defined as: acute peripheral vascular occlusion, amputation (non-traumatic; nondiabetic), cerebral arterial occlusion/cerebrovascular accident, cerebral venous occlusion, dermal thrombosis, gangrene (non-traumatic; nondiabetic), hepatic/portal vein thrombosis (Budd-Chiari syndrome), mesenteric/visceral arterial, thrombosis or infarction, mesenteric/visceral vein thrombosis or infarction, myocardial infarction, pulmonary embolus, renal arterial thrombosis, renal vein thrombosis, thrombophlebitis / deep vein thrombosis, transient ischemic attack, unstable angina or other
Time frame: Between Day 1 and Day 336
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LNP023 | Adjusted Annualized Major Adverse Vascular Events Rate After the Start of LNP023 Treatment | 0.00 MAVE events/year |
Other Pre-specified
Change From Baseline in Absolute Reticulocyte Count at Day 336
Change from baseline in absolute reticulocyte count at visit Day 336.
Time frame: Baseline, Day 336
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. Only participants with valid absolute reticulocyte count measurements at baseline and Day 336 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LNP023 | Change From Baseline in Absolute Reticulocyte Count at Day 336 | -76.55 x10^9 cells/L | Standard Deviation 50.149 |
Other Pre-specified
Change From Baseline in FACIT-Fatigue Score
The FACIT-Fatigue is a 13-item questionnaire with support for its validity and reliability in PNH that assesses patient self-reported fatigue and its impact on daily activities and function. All FACIT scales are scored so that a high score is better. As each of the 13 items of the FACIT-F Scale ranges from 0-4, the range of possible scores is 0-52, with 0 being the worst possible score and 52 the best.
Time frame: Baseline, Day 336
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned. Only participants with valid FACIT-Fatigue scores at baseline and Day 336 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LNP023 | Change From Baseline in FACIT-Fatigue Score | 10.4 score on a scale | Standard Deviation 10.14 |
Other Pre-specified
Change From Baseline in Hemoglobin Levels
Change from baseline in Hemoglobin at Visit Day 336
Time frame: Baseline, Day 336
Population: Full analysis set: All patients with confirmed eligibility to whom study treatment was assigned. Only participants with valid Hb measurements at Day 336 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LNP023 | Change From Baseline in Hemoglobin Levels | 5.09 g/dL | Standard Deviation 2.01 |
Other Pre-specified
Change From Baseline in LDH at Visit Day 336
Change from baseline in Lactate dehydrogenase (LDH) at Visit Day 336
Time frame: Baseline, Day 336
Population: Full Analysis Set (FAS): All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LNP023 | Change From Baseline in LDH at Visit Day 336 | -1393.3 U/L | Standard Deviation 652.15 |
Other Pre-specified
Marginal Proportion (Expressed as Percentage) of Patients Not Receiving and Not Requiring RBC Transfusions
Requiring Red Blood Cells (RBC) transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms).
Time frame: Between Day 14 and Day 336
Population: Full analysis set: All patients with confirmed eligibility to whom study treatment was assigned.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LNP023 | Marginal Proportion (Expressed as Percentage) of Patients Not Receiving and Not Requiring RBC Transfusions | 97.5 Percentage of participants |
Other Pre-specified
Percentage of Patients Meeting Hematological Response Criteria Irrespective of RBC Transfusions
Patients with hematological response are those with an increase in Hb from baseline ≥ 2g/dL irrespective of red blood cell (RBC) transfusions and patients achieving Hb ≥ 12g/dL irrespective of RBC transfusions.
Time frame: Baseline, Day 336
Population: Full analysis set: All patients with confirmed eligibility to whom study treatment was assigned. Only participants with valid Hb measurements at Day 336 were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LNP023 | Percentage of Patients Meeting Hematological Response Criteria Irrespective of RBC Transfusions | ≥2 g/dL increase in Hb from baseline irrespective of RBC transfusions | 97.4 Percentage of participants |
| LNP023 | Percentage of Patients Meeting Hematological Response Criteria Irrespective of RBC Transfusions | Hb ≥ 12g/dL irrespective of transfusions | 79.5 Percentage of participants |